Inhibitor regulation of tissue kallikrein activity in the synovial fluid of patients with rheumatoid athritis

Tissue kallikrein (TK) and 1-antitrypsin (AT)/TK complexes can be detected in SF from patients with RA if components of the fluids which interfere with the detection of TK are removed. 2-Macroglobulin (2-M) in SF was demonstrated to contain trapped proteases which were still active in amidase assays. Removal of 2-M from RA SF reduced their amidase activity. However, at least some of the remaining activity was due to TK because it was soya bean trypsin inhibitor resistant and trasylol sensitive and was partly removed by affinity chromatography on anti-TK sepharose. Removal of RF from the fluids reduced the values obtained for TK levels by ELISA. Addition of SF to human urinary kallikrein (HUK) considerably reduced the levels of TK detected suggesting the presence of a TK ELISA inhibitor in the fluids. Removal of components of >300 kDa from SF markedly reduced the TK ELISA inhibitory activity and increased the values for both the TK and l-AT/TK levels in fluids as measured by ELISA. It is considered this novel inhibitor does not bind to the active site of TK but rather binds to the site reactive with anti-TK antibodies

Risk of cancer in first seven years after metal-on-metal hip replacement compared with other bearings and general population: linkage study between the National Joint Registry of England and Wales and hospital episode statistics

Objective To determine whether use of metal-on-metal bearing surfaces is associated with an increased risk of a diagnosis of cancer in the early years after total hip replacement and specifically with an increase in malignant melanoma and haematological, prostate, and renal tract cancers

MOBILE and the provision of total joint replacement

Modern joint replacements have been available for 45 years, but we still do not have clear indications for these interventions, and we do not know how to optimize the outcome for patients who agree to have them done. The MOBILE programme has been investigating these issues in relation to primary total hip and knee joint replacements, using mixed methods research

The power of invalidating communication: Receiving invalidating feedback predicts threat-related emotional, physiological, and social responses

© 2016 Guilford Publications, Inc. Previous studies have found that communicating acceptance and understanding (validation) enhances the recipient's psychological and physiological wellbeing compared with receiving nonunderstanding feedback (invalidation). Yet, such studies have not established whether it is validation or absence of invalidation that is beneficial. This study examined the social, physiological, and emotional effects of validating and invalidating feedback in more detail, by employing a control group. Ninety healthy volunteers were randomly allocated to receive validating, invalidating, or no feedback during a series of stressor tasks. Self-report ratings, psychophysiological measurements and social engagement behaviors were recorded. While there were no significant differences between validated and control participants, invalidated participants showed increased physiological and psychological arousal on several measures and reduced social engagement behaviors compared with the other two groups. the relevance of these findings for understanding adverse effects of invalidation during clinical interactions is discussed

Evaluating elbow osteoarthritis within the prehistoric Tiwanaku state using generalized estimating equations (GEE).

OBJECTIVES:Studies of osteoarthritis (OA) in human skeletal remains can come with scalar problems. If OA measurement is noted as present or absent in one joint, like the elbow, results may not identify specific articular pathology data and the sample size may be insufficient to address research questions. If calculated on a per data point basis (i.e., each articular surface within a joint), results may prove too data heavy to comprehensively understand arthritic changes, or one individual with multiple positive scores may skew results and violate the data independence required for statistical tests. The objective of this article is to show that the statistical methodology Generalized Estimating Equations (GEE) can solve scalar issues in bioarchaeological studies. MATERIALS AND METHODS:Using GEE, a population-averaged statistical model, 1,195 adults from the core and one colony of the prehistoric Tiwanaku state (AD 500-1,100) were evaluated bilaterally for OA on the seven articular surfaces of the elbow joint. RESULTS:GEE linked the articular surfaces within each individual specimen, permitting the largest possible unbiased dataset, and showed significant differences between core and colony Tiwanaku peoples in the overall elbow joint, while also pinpointing specific articular surfaces with OA. Data groupings by sex and age at death also demonstrated significant variation. A pattern of elbow rotation noted for core Tiwanaku people may indicate a specific pattern of movement. DISCUSSION:GEE is effective and should be encouraged in bioarchaeological studies as a way to address scalar issues and to retain all pathology information

Clinical predictors of elective total joint replacement in persons with end-stage knee osteoarthritis

Abstract Background Arthritis is a leading cause of disability in the United States. Total knee arthroplasty (TKA) has become the gold standard to manage the pain and disability associated with knee osteoarthritis (OA). Although more than 400 000 primary TKA surgeries are performed each year in the United States, not all individuals with knee OA elect to undergo the procedure. No clear consensus exists on criteria to determine who should undergo TKA. The purpose of this study was to determine which clinical factors will predict the decision to undergo TKA in individuals with end-stage knee OA. Knowledge of these factors will aid in clinical decision making for the timing of TKA. Methods Functional data from one hundred twenty persons with end-stage knee OA were obtained through a database. All of the individuals complained of knee pain during daily activities and had radiographic evidence of OA. Functional and clinical tests, collectively referred to as the Delaware Osteoarthritis Profile, were completed by a physical therapist. This profile consisted of measuring height, weight, quadriceps strength and active knee range of motion, while functional mobility was assessed using the Timed Up and Go (TUG) test and the Stair Climbing Task (SCT). Self-perceived functional ability was measured using the activities of daily living subscale of the Knee Outcome Survey (KOS-ADLS). A logistic regression model was used to identify variables predictive of TKA use. Results Forty subjects (33%) underwent TKA within two years of evaluation. These subjects were significantly older and had significantly slower TUG and SCT times (p 2 = 0.403). Conclusions Younger patients with full knee ROM who have a higher self-perception of function are less likely to undergo TKA. Physicians and clinicians should be aware that potentially modifiable factors, such as knee ROM can be addressed to potentially postpone the need for TKA.</p

(Re)acting Medicine: applying theatre in order to develop a whole-systems approach to understanding the healing response.

This is an Accepted Manuscript of an article published by Taylor & Francis Group in Research in Drama Education: The Journal of Applied Theatre and Performance on 30/09/2014, available online: http://www.tandfonline.com/10.1080/13569783.2014.928007UK health and care provision is in crisis. Dominant practices, ideologies and infrastructure need to change. Our research team is investigating how performance-led research and creative practice is able to positively shape that change. Presently biomedicine holds the power; its reductionist research approach and acute medical model dominate. Neither are well-equipped to engage with increasing non-communicable, long-term, multi-issue, chronic ill-health. We believe that creative practitioners should be using their own well-established approaches to trouble this dominant paradigm to both form and inform the future of healing provision and wellbeing creation. Our transdisciplinary team (drama and medicine) is developing a methodology that is rooted in productive difference; an evolving synergy between two cultural and intellectual traditions with significant divergences in their world-view, perceptions, approaches and training methods. This commonality is underpinned by four assumptions that; (1) human-to-human interactions matter, (2) context matters, (3) the whole person and their community matters and (4) interpretation matters. Initially, we are using this methodology to investigate the fundamental human-to-human interaction of a person seeking healing (a healee) with a healer: we believe that this interaction enables the Healing Response - the intrinsic ability of the human organism to self-heal and regain homeostasis. In this paper we reflect on the project’s early stages

Osteoarthritis and functional disability: results of a cross sectional study among primary care patients in Germany

Contains fulltext : 52359.pdf ( ) (Open Access)BACKGROUND: The aim of the study was to determine factors associated with functional disability in patients with OA. METHODS: 1250 questionnaires were distributed to OA outpatients from 75 general practices; 1021 (81.6%) were returned. Questionnaires included sociodemographic data, the short form of the Arthritis Impact Measurement Scale (AIMS2-SF), and the Patient Health Questionnaire (PHQ-9) to assess concomitant depression. A hierarchical stepwise multiple regression analysis with the AIMS2-SF dimension "lower body" as dependent was performed. RESULTS: Main factors associated with functional disability were depression symptoms, as reflected in a high score of the PHQ-9 (beta = 0.446; p < 0.0009), pain as reflected in the AIMS2-SF symptom scale (beta = 0.412; p = 0.001), and few social contacts (beta = 0.201; p < 0.042). A high body mass index was associated with lower functional ability (beta = 0.332; p = 0.005) whereas a higher educational level (beta = -0.279; p = 0.029) predicted less impairment. Increased age was a weak predictor (beta = 0.178; p = 0.001) of disability. With a p of 0.062 the radiological severity according to the grading of Kellgren and Lawrence slightly surpassed the required significance level for remaining in the final regression model. CONCLUSION: The results emphasize that psychological as well as physical factors need to be addressed similarly to improve functional ability of patients suffering from OA. More research with multifaceted and tailored interventions is needed to determine how these factors can be targeted appropriately

Subjects with Knee Osteoarthritis Exhibit Widespread Hyperalgesia to Pressure and Cold

Hyperalgesia to mechanical and thermal stimuli are characteristics of a range of disorders such as tennis elbow, whiplash and fibromyalgia. This study evaluated the presence of local and widespread mechanical and thermal hyperalgesia in individuals with knee osteoarthritis, compared to healthy control subjects. Twenty-three subjects with knee osteoarthritis and 23 healthy controls, matched for age, gender and body mass index, were recruited for the study. Volunteers with any additional chronic pain conditions were excluded. Pain thresholds to pressure, cold and heat were tested at the knee, ipsilateral heel and ipsilateral elbow, in randomized order, using standardised methodology. Significant between-groups differences for pressure pain and cold pain thresholds were found with osteoarthritic subjects demonstrating significantly increased sensitivity to both pressure (p = .018) and cold (p = .003) stimuli, compared with controls. A similar pattern of results extended to the pain-free ipsilateral ankle and elbow indicating widespread pressure and cold hyperalgesia. No significant differences were found between groups for heat pain threshold, although correlations showed that subjects with greater sensitivity to pressure pain were also likely to be more sensitive to both cold pain and heat pain. This study found widespread elevated pain thresholds in subjects with painful knee osteoarthritis, suggesting that altered nociceptive system processing may play a role in ongoing arthritic pain for some patients